Treatment of various cancers increasingly involves cytoreductive therapy, including high dose chemotherapy or radiation therapy. These therapies decrease a patient's white blood cell counts, suppress bone marrow hematopoietic activity, and increase their risk of infection and/or hemorrhage. As a result, patients who undergo cytoreductive therapy must also receive therapy to reconstitute bone marrow function (hematopoiesis). Current treatments to manage the problems that result from prolonged bone marrow suppression include the reinfusion of a patient's own previously harvested peripheral blood precursor cells (PBPC). In such procedures, patients undergo successive treatments with cell mobilization agents to cause mobilization of hematopoietic progenitor cells from the bone marrow to the peripheral circulation for harvesting. After harvesting, the patient is given high dose chemotherapy or radiotherapy and the bone marrow function is reconstituted by infusion of the cells harvested earlier.
Because of the small number of PBPC present in the blood, multiple cycles of mobilization of PBPC (movement of PBPC from the hematopoietic organs into the peripheral circulation) are required to collect a sufficient number of PBPC for transplantation. This method is costly, inconvenient for outpatients, and may be associated with adverse side effects. Furthermore, mobilization of PBPC may take many days. G-CSF and GM-CSF have been used to release stem cells from marrow to be harvested before chemotherapy; however, the treatment takes from 4 to 7, and up to 12 days, before appearance of the cells in the peripheral blood (see published PCT application WO 94/38916). Furthermore, some patients fail to mobilize PBPC following treatment with colony-stimulating factors.
Development of a method to enhance and accelerate PBPC mobilization and facilitate hematopoietic reconstitution would be highly desirable, especially for individuals who require transplantation of PBPC following cytoreductive therapy.